Figure 6.

Aβ₄₂ activates the Dectin-1-Syk signaling pathway by binding to Dectin-1 and inducing its homodimerization. (A) BV2 cells are treated with 20 µM Bio- Aβ₄₂ or free biotin for 45 min, and cells are double-stained for biotin (green) and Dectin-1 (red) or Trem 2 (red), respectively. Nuclei are counterstained with DAPI (blue) [scale bar = 5 μm]. (B) Bio-Aβ₄₂ is added to streptavidin-agarose beads and incubated. Biotin alone was used as control. Lysates prepared from BV2 cells were added to beads. The eluent was loaded onto a polyacrylamide gel for western blot analysis. Total lysates were used as input controls. Trem2 was used as a positive control. (C) The Dectin-1-APP/ β-amyloid interaction is analyzed by co-immunoprecipitation in the brains of WT and model mice. (D) Surface plasmon resonance (SPR) analysis showing a direct interaction between Aβ₄₂ and rhDectin-1. Mean KD constant derived from five separate experiments. (E) 3D binding model of dectin-1 and amyloid beta peptide. The backbones of dectin-1 and amyloid beta peptide are shown as cartoons. The residues in dectin-1 are shown as cyan sticks, whereas the residues in amyloid beta-peptide are shown as wheat sticks. The hydrogen bonds are depicted as red dashed lines and the salt bridges are depicted as blue dashed lines.